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PMID:14764662

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Citation

Hamerman, JA, Ogasawara, K and Lanier, LL (2004) Cutting edge: Toll-like receptor signaling in macrophages induces ligands for the NKG2D receptor. J. Immunol. 172:2001-5

Abstract

Macrophages recognize the presence of infection by using the Toll-like receptor (TLR) family of proteins that detect ligands on bacterial, viral, and fungal pathogens. We show that murine macrophages stimulated with pathogen products known to signal through TLRs express ligands for the NKG2D receptor, found on NK cells, activated CD8(+) T cells and activated macrophages. TLR signaling, through the MyD88 adaptor, up-regulates transcription of the retinoic acid early inducible-1 (RAE-1) family of NKG2D ligands, but not H-60 or murine UL16-binding protein-like transcript-1. RAE-1 proteins are found on the surface of activated, but not resting, macrophages and can be detected by NKG2D on NK cells resulting in down-regulation of this receptor both in vitro and in vivo. RAE-1-NKG2D interactions provide a mechanism by which NK cells and infected macrophages communicate directly during an innate immune response to infection.

Links

PubMed

Keywords

Adaptor Proteins, Signal Transducing; Animals; Antigens, Differentiation/genetics; Antigens, Differentiation/physiology; Cells, Cultured; Escherichia coli/immunology; Ligands; Lipopolysaccharides/pharmacology; Listeria monocytogenes/immunology; Macrophage Activation; Macrophages, Peritoneal/immunology; Macrophages, Peritoneal/metabolism; Macrophages, Peritoneal/microbiology; Membrane Glycoproteins/physiology; Membrane Proteins/biosynthesis; Membrane Proteins/genetics; Membrane Proteins/metabolism; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Knockout; Myeloid Differentiation Factor 88; NK Cell Lectin-Like Receptor Subfamily K; Poly I-C/pharmacology; RNA, Messenger/biosynthesis; Receptors, Cell Surface/physiology; Receptors, Immunologic/deficiency; Receptors, Immunologic/genetics; Receptors, Immunologic/metabolism; Receptors, Immunologic/physiology; Receptors, Natural Killer Cell; Signal Transduction/immunology; Toll-Like Receptors; Tretinoin/metabolism; Zymosan/pharmacology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:RAE1A

acts_upstream_of_or_within

GO:0042742: defense response to bacterium

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:RAE1A

acts_upstream_of_or_within

GO:0071360: cellular response to exogenous dsRNA

ECO:0000314: direct assay evidence used in manual assertion

P

  • occurs_in:(CL:0000235)

Seeded From UniProt

complete

MOUSE:RAE1A

acts_upstream_of_or_within

GO:0071222: cellular response to lipopolysaccharide

ECO:0000314: direct assay evidence used in manual assertion

P

  • occurs_in:(CL:0000235)

Seeded From UniProt

complete

MOUSE:RAE1B

acts_upstream_of_or_within

GO:0042742: defense response to bacterium

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:RAE1B

acts_upstream_of_or_within

GO:0071360: cellular response to exogenous dsRNA

ECO:0000314: direct assay evidence used in manual assertion

P

  • occurs_in:(CL:0000235)

Seeded From UniProt

complete

MOUSE:RAE1B

acts_upstream_of_or_within

GO:0071222: cellular response to lipopolysaccharide

ECO:0000314: direct assay evidence used in manual assertion

P

  • occurs_in:(CL:0000235)

Seeded From UniProt

complete

MOUSE:RAE1C

acts_upstream_of_or_within

GO:0042742: defense response to bacterium

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:RAE1C

acts_upstream_of_or_within

GO:0071360: cellular response to exogenous dsRNA

ECO:0000314: direct assay evidence used in manual assertion

P

  • occurs_in:(CL:0000235)

Seeded From UniProt

complete

MOUSE:RAE1C

acts_upstream_of_or_within

GO:0071222: cellular response to lipopolysaccharide

ECO:0000314: direct assay evidence used in manual assertion

P

  • occurs_in:(CL:0000235)

Seeded From UniProt

complete

MOUSE:NKG2D

located_in

GO:0009897: external side of plasma membrane

ECO:0000314: direct assay evidence used in manual assertion

C

  • part_of:(CL:0000235)

Seeded From UniProt

complete

MOUSE:NKG2D

acts_upstream_of_or_within

GO:0050830: defense response to Gram-positive bacterium

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:NKG2D

acts_upstream_of_or_within

GO:0071222: cellular response to lipopolysaccharide

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:CD44

located_in

GO:0009897: external side of plasma membrane

ECO:0000314: direct assay evidence used in manual assertion

C

  • part_of:(CL:0000623)

Seeded From UniProt

complete

MOUSE:MYD88

acts_upstream_of_or_within

GO:0002755: MyD88-dependent toll-like receptor signaling pathway

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • occurs_in:(CL:0000235)

Seeded From UniProt

complete

MOUSE:KLRBC

located_in

GO:0009897: external side of plasma membrane

ECO:0000314: direct assay evidence used in manual assertion

C

  • part_of:(CL:0000623)

Seeded From UniProt

complete

MOUSE:CD44

part_of

GO:0009897: external side of plasma membrane

ECO:0000314: direct assay evidence used in manual assertion

C

part_of:(CL:0000623)

Seeded From UniProt

complete


See also

References

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